Regulation of renovascular resistance and blood flow represents a complex inter-relationship of multiple factors with recent interest centering about the role of prostaglandins, specifically prostaglandin E2 (PGE2) and postaglandin F2a (PGF2a). Previous communications have ignored the potential significance of thromboxane A2 (TXA2), a powerful vasoconstrictor, in the regulation of renal blood flow and vascular resistance. Yet, pilot studies have for the first time indicated that in ischemically damaged kidneys TXA2 may be the single most important prostaglandin in regulation of renovascular resistance. The importance of PGE2, prostacyclin (PGI2) and TXA2 in regulation of renovascular resistance in ischemically damaged kidneys is investigated in an ex vivo hypothermic continuously perfused dog kidney preparation using a plasma-free perfusate which eliminates the importance of vasoactive plasma humoral factors. An optimally removed non-ischemic kidney is monitored for changes in renal vascular resistance as affected by an ischemic kidney which is added to the system. Modification of the renovascular response by biochemical inhibition of prostaglandin synthesis in general and of TXA2 specifically is correlated with changes in concentration of PGE2, PGI2, and TXA2 or their stable end-products in the perfusate, urine, and renal vein effluent. Analyses include bioassay, gas chromatography-mass-spectroscopy and radioimmunoassay. Localization of prostaglandin or TXA2 activity to the ischemic and/or responding non-ischemic kidney is investigated by selective inhibition of prostaglandin synthesis in each kidney separately. Autotransplantation of treated kidneys will ascertain the effects of modifying prostaglandin and TXA2 synthesis on the ability of kidneys to immediately function after transplantation. This would have important implications in the management of stored cadaver kidneys prior to human transplantation. Replication of the studies in kidneys perfused with heparinized blood under normothermic conditions will involve a more complex interrelationship, but permit observations under more nearly normal physiologic conditions.